Diastereoselective method of preparing olefins by means of the horner-wadsworthemmons reaction, comprising the addition of a tris-(polyoxaalkyl)-amine sequestering agent

ABSTRACT

The invention relates to a process for the diastereoselective preparation of olefins via the Homer-Wadsworth-Emmons reaction, which consists in reacting at low temperature a phosphonate with a carbonyl derivative in the presence of a base in a suitable solvent, characterized in that a tris(polyoxaalkyl)amine sequestering reagent of formula (I): N—[CHR 1 —CHR 2 —O—(CHR 3 —CHR 4 —O) n —R 5 ] 3  (I), wherein: n is an integer between 0 and 10; R 1 , R 2 , R 3  and R 4  may be identical or different, and represent a hydrogen atom or an alkyl radical containing from 1 to 4 carbon atoms; R 5  represents a hydrogen atom, an alkyl or cycloalkyl radical containing up to 12 carbon atoms, a phenyl radical or a radical of formula —CμH2μ-Φ, or C m H 2m+1 -Φ-, with m being an integer between 1 and 12 and Φ being a phenyl radical; is added in an amount that is sufficient to increase the diastereoselectivity of the olefin.

The present invention relates to a process for the diastereoselectivepreparation of olefins via the Horner-Wadsworth-Emmons reaction, whichconsists in reacting at low temperature a phosphonate with a carbonylderivative in the presence of a base, in a suitable solvent.

The reaction involved is as follows:

The carbonyl compound (B) may be an aldehyde or a ketone, with thecondition that R₉ takes precedence over R₁₀ according to the Cahn Ingoldand Prelog rules. These rules are described, for example, in the bookentitled “Advanced Organic Chemistry” Reactions, Mechanisms, andStructure, third edition, Jerry March, John Wiley & sons, 1985, thecontent of pages 96 to 112 of which is incorporated by reference.

It is known practice from Tetrahedron Letters, Vol. 24, No. 41, pages4405-4408, 1983 to use in this reaction five equivalents of amacrocyclic complexing agent of particular crown ether type, 18-crown-6(18C6) to improve the diastereoselectivity of the olefin (C) obtained.

However, this crown ether has the drawback of being expensive, toxic andharmful to the environment. There was a need to find another means forimproving the diastereoselectivity of the olefin obtained without usingthis crown ether.

The Applicant has just discovered, unexpectedly, that the use of atris(polyoxaalkyl)-amine makes it possible to improve thediastereoselectivity in the Homer-Wadsworth-Emmons reaction to levelscomparable to those obtained with 18-crown-6.

Thus, one subject of the present invention is a process for thediastereoselective preparation of olefins (C) via theHomer-Wadsworth-Emmons reaction, which consists in reacting at lowtemperature a phosphonate (A) with a carbonyl derivative (B) in thepresence of a base, in a suitable solvent,

in which the compounds (A) (B) and (C) are such that:

Y represents an electron-withdrawing group known to those skilled in theart and chosen so as not to disrupt the Homer-Wadsworth-Emmons reaction.Among these groups, mention may be made especially of:

-   -   —CO₂R,    -   —CN,    -   —C(O)R,    -   —S(O)R,    -   —S(O)₂R,    -   —C(O)NRR′,    -   —N═CRR′,    -   —P(O)OROR′,    -   with R and R′ as defined below,

R₆ and R₇, taken independently, may be identical or different andrepresent:

-   -   a saturated or unsaturated, linear or branched aliphatic radical        containing from 1 to 24 carbon atoms, optionally substituted        with hetero atoms;    -   a saturated, unsaturated or aromatic, monocyclic or polycyclic        cycloaliphatic radical containing from 4 to 24 carbon atoms,        optionally substituted with hetero atoms;    -   a saturated or unsaturated, linear or branched aliphatic radical        bearing a cyclic substituent optionally substituted with hetero        atoms in the aliphatic part and/or the cyclic part;

R₁₀, R and R′, taken independently, may be identical or different andrepresent:

-   -   a hydrogen atom;    -   a saturated or unsaturated, linear or branched aliphatic radical        containing from 1 to 24 carbon atoms, optionally substituted        with hetero atoms;    -   a saturated, unsaturated or aromatic, monocyclic or polycyclic        cycloaliphatic radical containing from 4 to 24 carbon atoms,        optionally substituted with hetero atoms;    -   a saturated or unsaturated, linear or branched aliphatic radical        bearing a cyclic substituent optionally substituted with hetero        atoms in the aliphatic part and/or the cyclic part;

R₆, R₇, R and R′ may also be taken together to form a saturated,unsaturated or aromatic ring optionally comprising hetero atoms;

R₈ represents a radical chosen from:

-   -   —R,    -   a halogen atom,    -   —OR,    -   —NRR′,    -   with R and R′ as defined above,

R₉ represents a radical chosen from:

-   -   a saturated or unsaturated, linear or branched aliphatic radical        containing from 1 to 24 carbon atoms, optionally substituted        with hetero atoms;    -   a saturated, unsaturated or aromatic, monocyclic or polycyclic        cycloaliphatic radical containing from 4 to 24 carbon atoms,        optionally substituted with hetero atoms; the hetero atoms also        possibly being present in the cyclic part;    -   a saturated or unsaturated, linear or branched aliphatic radical        bearing a cyclic substituent optionally substituted with hetero        atoms in the aliphatic part and/or the cyclic part;        with the condition that R₉ takes precedence over R₁₀ according        to the Cahn Ingold and Prelog rules,        characterized in that a tris(polyoxaalkyl)amine sequestering        agent of formula (I):        N—[CHR₁—CHR₂—O—(CHR₃—CHR₄—O)_(n)—R₅]₃   (I)        in which:

n is an integer between 0 and 10;

R₁, R₂, R₃ and R₄ may be identical or different and represent a hydrogenatom or an alkyl radical containing from 1 to 4 carbon atoms;

R₅ represents a hydrogen atom, an alkyl or cycloalkyl radical containingup to 12 carbon atoms, a phenyl radical or a radical of formula—C_(m)H_(2m)Φ, or C_(m)H_(2m+1)-Φ-, with m being an integer between 1and 12 and Φ being a phenyl radical;

is added to the reaction medium in an amount that is effective toincrease the diastereo-selectivity of the olefins (C).

Preferably, the tris(polyoxaalkyl)amine sequestering agent used is oneof formula (I) in which:

R₁, R₂, R₃ and R₄ may be identical or different and represent a hydrogenatom or a methyl radical;

n is an integer between 0 and 3;

R₅ represents a hydrogen atom or an alkyl radical containing from 1 to 4carbon atoms.

Even more preferably, the tris(polyoxaalkyl)amine sequestering agentused is one of formula (I) in which:

R₁, R₂, R₃ and R₄ represent a hydrogen atom;

n is 1;

R₅ represents a methyl radical.

The tris(polyoxaalkyl)amine sequestering agent of formula (I) may beused in an amount ranging from 0.05 to 10 equivalents per 1 equivalentof phosphonate, one equivalent of aldehyde and one equivalent of base.

Preferably, the amount of tris(polyoxaalkyl)amine sequestering agent offormula (I) used is from 0.1 to 5 equivalents per 1 equivalent ofphosphonate, one equivalent of aldehyde and one equivalent of base.

Even more preferably, the amount of tris(polyoxaalkyl)amine sequesteringagent of formula (I) used is 1 equivalent per 1 equivalent ofphosphonate, one equivalent of aldehyde and one equivalent of base, thewhole being dissolved in a solvent.

The phosphonate used for the reaction may be chosen from phosphonates offormula (A): in which

Y represents CO₂R, with R representing a hydrogen atom or a linear,branched or cyclic, saturated or unsaturated alkyl radical containingfrom 1 to 12 carbon atoms,

R₆ and R₇ represent a —CH₂CF₃ radical, and R₈ represents a hydrogenatom.

Preferably, a phosphonate of formula (A) is used in which:

Y represents a radical CO₂R, and R represents a methyl radical;

R₆ and R₇ represents a —CH₂CF₃ radical; and R₈ represents a hydrogenatom.

The carbonyl derivative (B) used for the reaction may be an aldehyde ora ketone. The substituents R₉ and R₁₀ are, of course, chosen so as notto disrupt the Homer-Wadsworth-Emmons reaction. One condition accordingto the Cahn, Ingold and Prelog rule has been set, so as to define theselectivity of the olefin (C). The Cahn Ingold and Prelog rule isdescribed, for example, in the book entitled “Advanced OrganicChemistry” Reactions, Mechanisms, and Structure, third edition, JerryMarch, John Wiley & sons, 1985, the content of pages 96 to 112 of whichis incorporated by reference.

The carbonyl derivative (B) is preferably chosen from aldehydes, whichcorresponds to R₁₀ representing a hydrogen atom. The aldehydes used maybe, depending on the nature of the radical R₉, aliphatic, and optionallycomprise ethylenic unsaturations, or they may be aromatic. In the casewhere the aldehydes used are aromatic, they may comprise optionalsubstitutions with electron-donating or electron-withdrawing groups.Electron-donating groups that may be mentioned include C1-C6 alkyl,C1-C6 alkoxy and phenyl groups, where appropriate substituted with analkyl or alkoxy group as defined above.

For the purposes of the present invention, the term“electron-withdrawing group” means a groups as defined by H. C. Brown inthe book entitled “Advanced Organic Chemistry” Reactions, Mechanisms,and Structure, third edition, Jerry March, John Wiley & sons, 1985, thecontent of pages 243 and 244 of which is incorporated by reference.

Representative electron-withdrawing groups that may especially bementioned include:

-   -   a halogen atom    -   a group SO₂R with R as defined above    -   a CN or NO₂ group.

An aromatic aldehyde is preferably used.

Among the aliphatic aldehydes that may be mentioned arecyclohexanecarboxaldehyde (R₉ is a cyclohexyl radical) or an aliphaticaldehyde in which R₉ is n-C₇H₁₅. The aliphatic aldehyde in which R₉ is acyclohexyl radical is preferably used.

Among the aromatic aldehydes that may be mentioned are benzaldehyde (R₉represents a phenyl radical) or an aldehyde characterized in that theradical R₉ used is aromatic and optionally comprises one or moresubstitutions with alkoxy groups containing from 1 to 6 carbon atoms orhalogen atoms.

Examples that may also be mentioned include the aldehydes listed inTable VII.

Thus, the aromatic aldehyde may comprise hetero atoms in the aromaticring.

The aromatic aldehyde may also comprise substitutions with CF₃ groups.

The base is chosen from:

amides of the type MNR″R′″ with M being an alkali metal such as lithium,sodium or potassium, and R″, R′″ being chosen from alkyl radicals orradicals of alkylsilane type, such as the potassium salt ofhexamethyldisilazane (KHMDS),

alkoxides of the type MOR″ with M being an alkali metal such as lithium,sodium or potassium, and R″ being chosen from alkyl radicals, such aspotassium tert-butoxide (KOtBu),

hydrides of the type MH with M being an alkali metal such as lithium,sodium or potassium,

carbonates of the type M₂CO₃ or MCO₃, with M being an alkali metal suchas lithium sodium, potassium or cesium, or an alkaline-earth metal suchas calcium or barium,

alkali metal or alkaline-earth metal hydroxides such as LiOH, NaOH, KOH,CsOH, Mg(OH)₂, Ca(OH)₂ and Ba(OH)₂,

organic bases, for instance 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU),1,1,3,3-tetra-methylguanidine (TMG) or 1,4-diazabicyclo[2.2.2]octane(DABCO) in combination with alkali metal or alkaline-earth metalhalides.

The potassium salt of hexamethyldisilazane (KHMDS) or potassiumtert-butoxide (KOtBu) is preferably used.

The solvent used is an organic solvent. A polar solvent is preferablyused. Even more preferably, an ether solvent such as THF or methyltert-butyl ether (MTBE) is used.

The amount of solvent used is generally between 0.1 and 20 ml per mmolof phosphonate.

The improvement in the selectivity of the reaction in the presence ofthe sequestering agent of the invention is observed irrespective of thetemperature. The process of the invention may thus be performed at atemperature of 0° C. However, it is preferred to perform the process ofthe invention at a temperature of less than or equal to −20° C. and evenmore preferably at a temperature of less than or equal to −50° C.

As a guide, the reaction is generally performed at a temperature above−100° C.

Other aspects and advantages of the processes that are subjects of theinvention will become apparent in the light of the examples given belowas non-limiting illustrations.

EXAMPLE 1 Demonstration of the Effect of the Sequestering Agent TDA-1and Comparison with 18-crown-6 at −78° C.

In this example, the phosphonate used corresponds to a phosphonate offormula (A) in which:

Y represents a radical CO₂R with R representing a methyl radical,

R₆ and R₇ represent a —CH₂CF₃ radical; and

R₈ represents a hydrogen atom.

The carbonyl compound (B) used is benzaldehyde.

The base used is potassium hexamethyldisilazide (KHMDS) as a 0.5Msolution in toluene.

The solvent used is THF.

The sequestering agent of the invention used, known as TDA-1,corresponds to a tris(polyoxaalkyl)amine sequestering agent of formula(I) in which:

R₁, R₂, R₃ and R₄ represent a hydrogen atom;

-   -   n is 1;    -   R₅ represents a methyl radical.

Procedure:

1 mmol of phosphonate, 1.1 mmol of TDA-1 or 5 mmol of 18-crown-6 and 20ml of anhydrous THF are introduced into a 100 ml one-necked flask. Themixture is then cooled using a bath of cardice and acetone. Afterstirring for thirty minutes at −78° C., 2 ml of a 0.5M solution of KHMDSin toluene are added dropwise. After stirring for a further thirtyminutes, 1.1 mmol of benzaldehyde are added.

After about 2 hours at −78° C., the reaction is quenched by addition ofsaturated ammonium chloride solution and the mixture is extracted withtoluene.

The mixture is analyzed by gas chromatography using a Varian Star 3400CXmachine. The column used is a DB1 125-1034 from J&W Scientific (length:30 m, inside diameter: 0.53 mm and film thickness of 3 μm). The initialcolumn temperature is 100° C. and the temperature rise is 7° C. perminute. Under these conditions, the retention times of the variouscompounds are as follows:

benzaldehyde: 4.5 minutes

phosphonate: 5.9 minutes

Z isomer: 10.2 minutes

E isomer: 11.6 minutes

The diastereoselectivity factor S (S=Z/(Z+E) in %) is defined by thesurface area ratio of the amount of Z isomer to the sum of the Z and Eisomers formed.

The Z and E isomers are defined in the boxed reaction scheme on theprevious page. In the present case, the role of the additive is toimprove the selectivity of Z isomer.

The conversion (Conv=(Z+E)/(Z+E+phosphonate) in %) is also defined bythe surface area ratio of the amount of olefin formed to the sum of theamounts of olefin formed and of residual phosphonate.

The diastereoselectivities obtained, without addition of sequesteringagent, with addition of sequestering agent of the invention and withaddition of 18-crown-6, at −78° C., are compared in Table I. TABLE IAdditive Conv (%) S (%) none 99 92 18-C-6 93 98 TDA-1 94 98

The results obtained show the effect of the sequestering agent on thediastereoselectivity S expressed in %.

A diastereoselectivity of 98%, which is identical to that observed with18-crown-6, is obtained with the sequestering agent of the inventionknown as TDA-1 at −78° C. The effect of TDA-1 is noted since theselectivity is only 92% without additive.

EXAMPLE 2 Evaluation of the Conditions of Example 1 (THF, KHMDS, TDA-1,−78° C.) with cyclohexanecarboxaldehyde

In this example, the procedure of example 1 is repeated and the natureof the aldehyde used is varied. The benzaldehyde is replaced withcyclohexanecarboxaldehyde (R₉ represents a cyclohexyl radical). Thetemperature is maintained at −78° C. for about 4 hours before allowingthe system to return to room temperature overnight. The reaction mediumis then worked up by addition of saturated ammonium chloride solutionand extraction with toluene.

As in example 1, the mixture is analyzed by gas chromatography using aVarian Star 3400CX machine. The column used is a DB1 125-1034 from J&WScientific (length: 30 m, inside diameter: 0.53 mm and film thickness of3 μm). The initial column temperature is 100° C. and the temperaturerise is 7° C. per minute. Under these conditions, the retention times(t_(R)) of the various compounds are as follows: TABLE II Compound t_(R)(min)

4.3

8.9

10.6

The selectivities obtained with TDA-1 and 1 8-crown-6 are indicated inTable III TABLE III Cyclohexanecarboxaldehyde Additive Conv (%) S (%)18-C-6 78 81 TDA-1 100 81

It is observed that identical selectivities are obtained with TDA-1 and18-crown-6.

EXAMPLE 3 Effect of Concentration Under the Conditions of Example 1(THF, KHMDS TDA-1, −78° C., benzaldehyde)

The procedure of example 1 is repeated with TDA-1 and several tests areperformed, reducing the amount of THF used.

The tests are performed with, respectively, 20 ml of THF (volume ofexample 1), 4 ml of THF, 2 ml of THF and without THF. This correspondsto phosphonate concentrations of 0.05M, 0.15M, 0.21M and 0.41M.

The results obtained are indicated in Table IV below. TABLE IV C (M)Conv (%) S (%) 0.05 97 98 0.15 100 98 0.21 100 98 0.41 76 77

The results obtained show that the concentration does not affectselectivity in the range 0.05-0.21M.

At 0.41M, the toluene of the KHMDS solution is the reaction solvent. Theconversion is much slower and much less selective.

This shows the influence of the solvent on the diastereoselectivity ofthe reaction.

EXAMPLE 4 Use of Potassium Tert-Butoxide as Base Under the Conditions ofExample 1 (THF, TDA-1, −78° C.)

Procedure:

1.05 mmol of KOTBu, 1.1 mmol of TDA-1 and 20 ml of anhydrous THF areintroduced into a 100 ml one-necked flask. The solution is stirred forthirty minutes at room temperature. The mixture is then cooled using abath of cardice and acetone. After stirring for thirty minutes at −78°C., 1 mmol of phosphonate is added dropwise. After stirring for afurther thirty minutes, 1.1 mmol of aldehyde are added.

The temperature is maintained at −78° C. for about 4 hours, and thesystem is then allowed to return to room temperature overnight. Thereaction medium is then worked up by addition of saturated ammoniumchloride solution and extraction with toluene.

The results obtained are collated in the table below. TABLE V AldehydeConv (%) S (%) Benzaldehyde 100 98 Cyclohexanecarboxaldehyde 100 82

The results obtained show that the selectivities towards Z isomersobtained with KOtBu are very similar to the selectivities obtained withKHMDS for the two aldehydes tested (cf. examples 1 and 2).

EXAMPLE 5 Effect of Concentration Under the Conditions of Example 4(benzaldehyde, THF, KOtBu, TDA-1, −78° C.)

The procedure of example 4 is repeated with benzaldehyde, and severaltests are performed, reducing the amount of THF used. The tests areperformed with, respectively, 20 ml of THF (volume of example 4), 4 mlof THF, 2 ml of THF and 1 ml of THF. This corresponds to phosphonateconcentrations of 0.05M, 0.21M, 0.37M and 0.60M.

The results obtained are indicated in Table VI below. TABLE VI C (M)Conv (%) S (%) 0.05 84 98 0.21 91 96 0.37 99 94 0.60 99 94

EXAMPLE 6

General procedure: 5.5 mmol of phosphonate identical to the phosphonateof example 1, 5.5 mmol of TDA-1 and 90 ml of anhydrous THF areintroduced into a 250 ml round-bottomed flask. The mixture is thencooled using a bath of cardice and acetone. After stirring at −78° C.for 30 minutes, 10.5 ml of a 0.5M solution of KHMDS in toluene areadded. After stirring for a further 30 minutes, 5 mmol of aldehyde areadded and the medium is stirred at −78° C.

As regards entries 1, 2, 3, 4 and 7, the medium is worked up afterreaction at −78° C. for 4 hours. For entries 5, 6 and 8, since thealdehydes are less reactive, the medium is allowed to return to roomtemperature overnight before work-up.

Work-up: The mixture is diluted with 70 ml of methyl tert-butyl ether(MTBE) and quenched with 50 ml of saturated aqueous NH₄Cl solution. Theaqueous phase is re-extracted twice with 20 ml of MTBE and the combinedorganic phases are washed until neutral. After drying over Na₂SO₄, thesolvent is evaporated off under vacuum and the mixture of Z+E olefins ispurified by flash chromatography (mixture of cyclohexane and ethylacetate). The yields indicated in the table below are thus isolatedyields. The selectivity is determined by integration on the vinylprotons in proton NMR and in accordance with measurements taken by gaschromatography. TABLE VII Entry Aldehyde S (%) Yield (%) 1

99 95 2

98 90 3

99 91 4

98 95 5

93 92 6

93 95 7

98 93 8

92 97

1-21. (canceled) 22- A process for the diastereoselective preparation ofolefins (C) via the Homer-Wadsworth-Emmons reaction, comprising the stepof reacting at low temperature a phosphonate (A) with a carbonylderivative (B) in the presence of a base, in a suitable solvent to forma reaction medium,

in which the compounds (A) (B) and (C) are such that: Y represents anelectron-withdrawing group of the formula: —CO₂R, —CN, —C(O)R, —S(O)R,—S(O)₂R, —C(O)NRR′, —N═CRR′, or —P(O)OROR′, with R and R′ as definedbelow, R₆ and R₇, taken independently, are identical or different andrepresent: a saturated or unsaturated, linear or branched aliphaticradical containing from 1 to 24 carbon atoms, optionally substitutedwith hetero atoms; a saturated, unsaturated or aromatic, monocyclic orpolycyclic cycloaliphatic radical containing from 4 to 24 carbon atoms,optionally substituted with hetero atoms; or a saturated or unsaturated,linear or branched aliphatic radical bearing a cyclic substituentoptionally substituted with hetero atoms in the aliphatic part and/orthe cyclic part; R₁₀, R and R′, taken independently, are identical ordifferent and represent: a hydrogen atom; a saturated or unsaturated,linear or branched aliphatic radical having from 1 to 24 carbon atoms,optionally substituted with hetero atoms; a saturated, unsaturated oraromatic, monocyclic or polycyclic cycloaliphatic radical having from 4to 24 carbon atoms, optionally substituted with hetero atoms; or asaturated or unsaturated, linear or branched aliphatic radical bearing acyclic substituent optionally substituted with hetero atoms in thealiphatic part and/or the cyclic part; R₆, R₇, R and R′ taken togetheroptionally form a saturated, unsaturated or aromatic ring optionallycomprising hetero atoms; R₈ represents a radical of the formula: —R, ahalogen atom, —OR, or —NRR′, with R and R′ as defined above, R₉represents a radical of the formula: a saturated or unsaturated, linearor branched aliphatic radical having from 1 to 24 carbon atoms,optionally substituted with hetero atoms; a saturated, unsaturated oraromatic, monocyclic or polycyclic cycloaliphatic radical having from 4to 24 carbon atoms, optionally substituted with hetero atoms; the heteroatoms also possibly being present in the cyclic part; or a saturated orunsaturated, linear or branched aliphatic radical bearing a cyclicsubstituent optionally substituted with hetero atoms in the aliphaticpart and/or the cyclic part; with the further proviso that R₉ takesprecedence over R₁₀ according to the Cahn Ingold and Prelog rules, andwherein a tris(polyoxaalkyl)amine sequestering agent of formula (I):N—[CHR₁—CHR₂—O—(CHR₃—CHR₄—O)_(n)—R₅]₃   (I) in which: n is an integerbetween 0 and 10; R₁, R₂, R₃ and R₄ are identical or different andrepresent a hydrogen atom or an alkyl radical having from 1 to 4 carbonatoms; and R₅ represents a hydrogen atom, an alkyl or cycloalkyl radicalcontaining up to 12 carbon atoms, a phenyl radical or a radical offormula —C_(m)H_(2m)-Φ, or C_(m)H_(2m+1)-Φ-, with m being an integerbetween 1 and 12 and Φ being a phenyl radical; is being added to thereaction medium in an amount that is effective to increase thediastereoselectivity of the olefins (C). 23- The process as claimed inclaim 22, wherein the tris(polyoxaalkyl)amine sequestering agent is atris(polyoxaalkyl)amines of formula (I) wherein: R₁, R₂, R₃ and R₄represent a hydrogen atom or a methyl radical; n is an integer between 0and 3; and R₅ represents a hydrogen atom or an alkyl radical having from1 to 4 carbon atoms. 24- The process as claimed in claim 23, wherein informula (I): R₁, R₂, R₃ and R₄ represent a hydrogen atom; n is 1; and R₅represents a methyl radical. 25- The process as claimed in claim 22,wherein the tris(oxaalkyl)amine sequestering agent of formula (I) isused in an amount of between 0.05 and 10 equivalents per 1 equivalent ofphosphonate, one equivalent of aldehyde and one equivalent of base. 26-The process as claimed in claim 25, wherein the amount oftris(oxaalkyl)amine sequestering agent of formula (I) used is Iequivalent of tris-(oxaalkyl)amine sequestering agent of formula (I) per1 equivalent of phosphonate, one equivalent of aldehyde and oneequivalent of base, the whole being dissolve in the solvent. 27- Theprocess as claimed in claim 22, wherein in formula (A): Y representsCO₂R, with R representing a hydrogen atom or a linear, branched orcyclic, saturated or unsaturated alkyl radical alkyl having from 1 to 12carbon atoms, R₆ and R₇ represent a —CH₂CF₃ radical, and R₈ represents ahydrogen atom. 28- The process as claimed in claim 22, wherein informula (A): Y represents CO₂R, with R representing a methyl radical, R₆and R₇ represent a —CH₂CF₃ radical, and R₈ represents a hydrogen atom.29- The process as claimed in claim 22, wherein the carbonyl derivativeis an aldehyde, with R₁₀ representing a hydrogen atom. 30- The processas claimed in claim 29, wherein R₉ is an aliphatic radical, optionallyhaving ethylenic unsaturations. 31- The process as claimed in claim 9,wherein the radical R₉ is cyclohexyl. 32- The process as claimed inclaim 9, wherein R₉ is aromatic, optionally having one or moresubstitutions with alkoxy groups having from 1 to 6 carbon atoms,halogen atoms or CF₃ groups. 33- The process as claimed in claim 32,wherein the radical R₉ is a phenyl radical. 34- The process as claimedin claim 22, wherein the base used is: an amide of the formula: MNR″R′″with M being an alkali metal, and R″, R′″ being alkyl or alkylsilaneradicals, an alkoxide of the formula: MOR″ with M being an alkali metaland R″ being an alkyl radical, an hydride of the formula: MH with Mbeing an alkali metal, a carbonate of the formula: M₂CO₃, with M beingan alkali metal or an alkaline-earth metal, an alkali metal oralkaline-earth metal hydroxide, or an organic base, in combination withalkali metal or alkaline-earth metal halides. 35- The process as claimedin claim 34, wherein the base is the potassium salt ofhexamethyldisilazane (KHMDS) and potassium tert-butoxide (KOtBu). 36-The process as claimed in claim 22, wherein the solvent is a polarsolvent. 37- The process as claimed in claim 36, wherein the solventused is an ether solvent. 38- The process as claimed in claim 37,wherein the solvent used is tetrahydrofuran (THF) or methyl tert-butylether (MTBE). 39- The process as claimed in claim 36, wherein thesolvent is used in an amount of between 0.1 and 20 ml per mmol ofphosphonate (A). 40- The process as claimed in claim 22, wherein thereaction medium is maintained at a temperature of less than or equal to0° C. 41- The process as claimed in claim 40, wherein the temperature ismaintained at a temperature of less than or equal to −20° C. 42- Theprocess as claimed in claim 41, wherein the temperature is maintained ata temperature of less than or equal to −50° C.